Dissecting Causal Relationships Between Plasma Metabolites and Osteoporosis:A Bidirectional Mendelian Randomization Study

Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.

DESIGN OF NOVEL HIGH PRESSURE-RESISTANT HYDROTHERMAL FLUID SAMPLE VALVE

Sampling study is an effective exploration method, but the most extreme environments of hydrothermal vents pose considerable engineering challenges for sampling hydrothermal fluids. Moreover, traditional sampler systems with sample valves have difficulty in maintaining samples in situ pressure. However, decompression changes have effect on microorganisms sensitive to such stresses. To address the technical difficulty of collecting samples from hydrothermal vents, a new bidirectional high pressure-resistant sample valve with balanced poppet was designed. The sample valve utilizes a soft high performance plastic ＂PEEK＂ as poppet. The poppet with inapposite dimension is prone to occur to plastic deformation or rupture for high working pressure in experiments. To address this issue, based on the fmite element model, simulated results on stress distribution of the poppet with different structure parameters and preload spring force were obtained. The static axial deformations on top of the poppet were experimented. The simulated results agree with the experimental results. The new sample valve seals well and it can withstand high working pressure.